Fig. 17.24 ). When endothelial cells are stimulated by acetylcholine or other vasodilator agents (e.g., adenosine triphosphate [ATP], bradykinin, serotonin, substance P, histamine), NO is released. These agents do not cause vasodilation in blood vessels lacking the endothelium. NO (synthesized from L-arginine) activates guanylyl cyclase in vascular smooth muscle to increase the concentration of cyclic guanosine monophosphate (cGMP), which produces relaxation by decreasing myofilament sensitivity to [Ca++]. Release of NO can be stimulated by the shear stress of blood flow on the endothelium. The drug nitroprusside also increases cGMP by acting directly on vascular smooth
Acetylcholine also stimulates the release of an endothelium-dependent hyperpolarizing factor that underlies the relaxation of adjacent smooth muscle. Although arachidonic acid metabolites have been suggested, the factor remains unknown. Moreover, how the factor reaches vascular smooth muscle (diffusion through the extracellular space or passage via myoepithelial junctions) is unclear. Nevertheless, there are diverse ways by which endothelial cells communicate with vascular smooth muscle.
The endothelium can also synthesize endothelin, a potent vasoconstrictor peptide. Endothelin affects vascular tone and blood pressure and may be involved in pathological states, including atherosclerosis, pulmonary hypertension, congestive heart failure, and renal failure.
Passive Role of the Capillary Endothelium
Solvent and solute move across the capillary endothelial wall by three processes: diffusion, filtration, and pinocytosis. Diffusion is the most important process for transcapillary exchange, and pinocytosis is the least important.
Diffusion. Under normal conditions, only approximately 0.06 mL of water per minute moves across the capillary wall per 100 g of tissue as a result of filtration. In contrast, 300 mL of water per minute per 100 g of tissue moves across the capillary wall by diffusion. Thus diffusion is the key factor in providing exchange of gases, substrates, and waste products between capillaries and tissue cells.
The process of diffusion is described by Fick’s law (see also
Equation 17.17
J = quantity of a substance moved per unit time
A = cross-sectional area of the diffusion pathway
ΔC = concentration gradient of the solute •Fig. 17.25 Flowand Diffusion-Limited Transport From Capillaries (Cap) to Tissue. A, Flow-limitedtransport.Thesmallestwater-solubleinerttracerparticles(blue dots) reachnegligibleconcentrationsafterpassingonlyashortdistancedownthecapillary.Largerparticles(brown dots) withsimilarpropertiestravelfartheralongthecapillarybeforereachinganinsignificantintracapillaryconcentration.Bothsubstancescrosstheinterstitialfluid(ISF)andreachtheparenchymaltissue(Cell).Becauseoftheirsize,moreofthesmallerparticlesaretakenupbythetissuecells.Thelargestparticles(red circles) cannotpenetratethecapillaryporesandhencedonotescapefromthecapillarylumenexceptbypinocytoticvesicletransport.Anincreaseinthevolumeofbloodfloworanincreaseincapillarydensityincreasestissuesupplyofthediffusiblesolutes.Notethatcapillarypermeabilityisgreateratthevenousendofthecapillary(alsointhevenule,notshown)becauseofthelargernumberofporesinthisregion.B, Diffusion-limitedtransport.Whenthedistancebetweencapillariesandparenchymaltissueislargeasaresultofedemaorlowcapillarydensity,diffusionbecomesalimitingfactorinsolutetransportfromcapillarytotissue,evenathighratesofcapillaryflow.